Various publications, including patents, published applications, technical articles and scholarly articles are cited throughout the specification. Each of these cited publications is incorporated by reference herein, in its entirety.
Oral delivery of biologically active substances a preferred way to administer drugs to humans. In general, other methods of delivery, such as nasal, transdermal, buccal, injectable and other, are only used for special situations and when oral delivery is not possible. However, oral delivery of drugs is subject to two limitations. First, pertaining particularly to oral delivery, drugs ingested are passed through the gastrointestinal tract within 24 hours and sometimes in a few hours after ingestion. The second limitation, which pertains to oral and parenteral delivery, is that the half life of most drugs is less than a day and usually no more than a few hours. Thus it is very difficult for a standard immediate release single oral dose of a drug to be effective for more than 24 hours and in most cases more than several hours. A standard immediate release formulation is one that is designed to release the drug immediately upon dissolution in the gastrointestinal tract. As a matter of fact, a whole industry has developed around controlled or extended release of drugs, with a major objective to extend the therapeutic life of drugs from a few hours to even one day. These extended release formulations use different technologies to slowly release the drug as it travels through the gastrointestinal tract. For example Elan, Depomed, Alza, Biovail, Pennwest and Kos Pharmaceuticals are some of the companies that have developed such technologies, based on polymer coatings, hydrogels, polymer foams, osmotic pressure, and other technologies (for a review, see Rosen, H. & T. Arbribat, 2005, Nat. Rev. Drug Discovery, published online Apr. 22, 2005, doi:10.1038/nrd1721). Other research has focused on the development of prodrugs designed to improve physicochemical, biopharmaceutical or pharmokinetic properties of drugs, including controlling or extending drug release in the body (for a review, see J. Rautio, et al., 2008, Nat. Rev. Drug Discovery Volume 7, March 2008, 255-270).
Notwithstanding the technical advances referred to above, a single dose of an immediate or extended release orally delivered formulation of a drug is almost never effective for more than a day, save a handful of drugs that have very long half lives. Thus, there is a need in the art to develop drug compositions and methods of manufacture that are able to extend the delivery of a single drug dose to beyond one day, and preferably to multiple days. This invention addresses those needs.